Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver but is rare in the paediatric age group; thus, it may be misdiagnosed as the more common tumour, hepatoblastoma. Management varies in both these tumours, and pathological diagnosis thus plays an important role for definitive therapy. Only a few case reports available in the literature have described the cytological characteristics of paediatric HCC. The present study was thus planned to evaluate the cytomorphological features of paediatric HCC. METHODS: Cases diagnosed with HCC on ultrasound-guided fine needle aspiration cytology over a period of 14 years were retrieved. The cases were evaluated for detailed cytological features including cellularity, architecture, sinusoidal wrapping, trabecular thickness, necrosis, anisonucleosis, chromatin, nucleoli, nuclear contours, bi- or multinucleation, intranuclear and intracytoplasmic inclusions, naked nuclei, extra-medullary haematopoiesis, monomorphism, and nuclear overlapping. RESULTS: Twelve cases of HCC were included in the study. The median age at diagnosis was 10 years. Serum alpha-fetoprotein level was raised in most of them. Five of the 12 cases were characterised as moderately differentiated, three as poorly differentiated, two as well differentiated, and two as the fibrolamellar type of HCC. Cytohistological correlation was performed in seven cases. CONCLUSIONS: Ultrasound-guided fine needle aspiration serves as a useful tool to diagnose paediatric HCC and differentiate it from other primary hepatic malignancies, especially hepatoblastoma which closely mimics HCC in this age group, as serum alpha protein levels and imaging findings are unable to distinguish these two tumours.

Intracardiac Teratoma in a Child: A Rare Site of a Common Tumor.

Primary intracardiac teratoma is a rare cardiac tumor with few cases reports in neonates and children. The authors present a case of an 8-year-old boy diagnosed with a cystic mass within the heart. The mass lesion was originating from the interventricular septum and was obliterating the ventricular chambers. Clinically, the mass was suspected to be a hydatid cyst. Surgical excision of the cyst was done that was confirmed histopathologically as mature teratoma. Although rare, it should be considered in the differential diagnosis of cystic lesions of heart when evaluating mass lesions in the pediatric age group.

Langerhans cell histiocytosis presenting as a rapidly evolving frontotemporal syndrome.

Langerhans cell histiocytosis (LCH) is a rare disorder in adults which usually manifests with involvement of multiple organ systems, including the central nervous system. We describe an unusual case of biopsy-proven LCH presenting with frontotemporal-dominant cognitive impairment with hypothalamic involvement, along with multisystem disease. We propose that the dementia was probably an immune-mediated process triggered by LCH which responded dramatically to high-dose steroids.

Primary intracranial malignant ectomesenchymoma in an adult: Report of a rare case and review of the literature.

Malignant ectomesenchymoma (MEM) is an exceedingly rare rapidly progressing tumor of soft tissues of the central nervous system, believed to be derived from neural crest cells. The majority of cases have been observed in young children or adolescents. So far only 11 patients with intracranial manifestations (with confirmed clinicopathological data) have been documented. We report the first case of adult intracranial MEM in a 54-year-old man who presented with a 4 months history of headache and weakness of right side of the body. Magnetic resonance imaging showed a homogenously enhanced dural-based lesion in the left fronto-temporo-parietal lobe with significant perilesional edema and mass effect. No metastatic disease was identified and the lesion was grossly resected. Histopathological and immunohistochemical examination revealed mature and immature neurons and bizarre astrocytes admixed with a mesenchymal spindle cell (rhabdomyoblastic) component. Specific risk factors that contribute toward the development of MEM are unknown. Due to the scarcity of reported cases the role of adjuvant therapy is unclear.

Anaplastic Carcinoma Thyroid in a Young Child - an Extremely Rare Occurrence.

Anaplastic thyroid carcinoma (ATC), one of the most aggressive malignancies, is extremely rare in childhood. We present a case of 5-yearold child who presented with rapidly progressing thyroid swelling and stridor, for which she underwent emergency tracheostomy and biopsy. Histopathological features were suggestive of ATC and the patient died within two months after diagnosis. ATC, though very rare in childhood, should be kept in the differential diagnoses of rapidly enlarging neck masses in children. To the best of our knowledge, this is the youngest case of ATC reported in literature.

SMARCA4-deficient Undifferentiated Uterine Sarcoma: Clinicopathological Features of an Emerging Entity.

SMARCA4-deficient undifferentiated uterine sarcoma is a recently described molecularly defined entity among the subset of aggressive undifferentiated uterine tumors. Mutation in the SMARCA4 gene is a key driver alteration, as also seen in small cell carcinoma of ovary, hypercalcemic type (SCCOHT) and thoracic undifferentiated carcinoma. Limited number of cases of SMARCA4-deficient undifferentiated uterine sarcoma has been reported in literature. We hereby describe a case of this distinct entity in a 52-year-old woman. Histomorphological examination showed sheets of monomorphic epithelioid cells with a variable proportion of cells displaying rhabdoid features, brisk mitotic activity, and lymphovascular invasion. A panel of immunohistochemical markers was required to exclude the differential diagnoses. The tumor was microsatellite stable. Loss of SMARCA4 expression and intact expression of INI1 in tumor cells by immunohistochemistry (IHC) confirmed the diagnosis of SMARCA4- deficient undifferentiated uterine sarcoma. The patient had a rapidly progressive clinical course.

Cutaneous Adnexal Tumours: A Study of 395 Cases from a Tertiary Care Hospital.

Background: Cutaneous adnexal tumours (CATs) are one of the commonest clinical presentations in dermatology outpatients. They constitute a subset of skin tumours with a common clinical presentation and variable histological findings. Almost all of them clinically present as a subcutaneous nodule. Depending upon the site and distribution, the clinician can suspect the diagnosis. However, histopathological examination is the gold standard for the definitive diagnosis and proper subtyping of CATs. Aims: The present study is conducted to see the overall spectrum, incidence and distribution of CATs in a large cohort at the tertiary care centre with their clinical profile. Methods: This was a retrospective study in which all the CATs diagnosed over a period of 5 years (2015 to 2019) in a tertiary care hospital were studied. Clinical data were recorded from the histopathology requisition forms. Results: Three hundred and ninety-five cases of CATs were retrieved. Approximately 90% of cases were benign and 10% were malignant. The age of presentation ranged from 8 months to 81 years with male preponderance in all the histological subtypes. The most common site was the head and neck followed by the extremities. Morphologically, the maximum cases showed a differentiation towards sweat glands (44%), followed by sebaceous (29%), follicular (26.5%) and apocrine differentiation (5.3%). Malignant tumours were common in the elderly age group with sebaceous carcinoma being the commonest. Conclusion: CATs comprise of a wide spectrum of tumours occurring in all age groups. Malignant CATs are rare and common in older age groups. Histopathological examination is the gold standard in distinguishing between the different subtypes.

An unusual testicular mass in a young male: Metastasis from occult gastric carcinoma.

Metastases to the testis are uncommon. Signet-ring cell carcinomas from the gastrointestinal tract (GIT) can rarely disseminate to the testicles, mimicking primary testicular malignancies with signet-ring cells. We hereby describe a case of a 26-year-old male who presented with left testicular swelling, multiple lymphadenopathies, and normal serum tumor markers. Lymph node biopsy revealed clusters and singly lying signet-ring cells. Judicious use of immunohistochemistry confirmed the tumor to be GIT primary. Further investigations confirmed a gastric tumor extending to the duodenum. Although rare, metastatic tumors to the testis should be considered in differential diagnoses of testicular masses in a young patient, particularly when serum germ cell tumor markers are normal or mildly deranged.

Atrophic Kidney Like Lesion: A Provisional Entity With Brief Review of Literature.

Atrophic kidney-like lesion (AKLL) is a provisional renal entity with distinct morphological and immunohistochemical features. It characteristically resembles thyroid-like follicular renal cell carcinoma (RCC) of kidney, an emerging renal entity. Very few patients of AKLL have been reported in the literature. We are hereby describing the clinicopathological features of AKLL in a 38-year-old man. The patient was incidentally found to have a renal mass and underwent radical nephrectomy. The morphological and immunohistochemical findings revealed features of AKLL. The patient on 24 months' post-operative period follow-up is alive without recurrence or metastasis.

Detection of cardiac allograft vasculopathy on dual source computed tomography in heart transplant recipients: comparison with invasive coronary angiography.

OBJECTIVE: We aimed to evaluate the diagnostic accuracy (DA) of dual-source CT coronary angiography (DSCTCA) against invasive coronary angiography (ICA) in assessing stenotic cardiac allograft vasculopathy (CAV) in heart transplant (HTX) recipients. METHODS: Consecutive HTX recipients(n = 38) on annual surveillance, underwent DSCTCA prior to ICA on a 192-detector 384-slice DSCT scanner. Cases were classified as no CAV (no stenosis), any CAV (any degree of stenosis) or significant CAV (>50% stenosis). RESULTS: Mean age was 33.66 ± 11.45 years (M:F = 27:11, median time from HTX-23.5 months). Prevalence of any CAV on DSCTCA and ICA was 44.7%(n = 17) and 39.5%(n = 15), respectively and that of significant CAV was 21.1%(n = 8) and 15.8%(n = 6), respectively. 557 (96.7%) segments were interpretable on DSCTCA. Mean radiation dose was 4.24 ± 2.15 mSv. At patient-level, the sensitivity, specificity, positive-predictive value, negative-predictive value (NPV), and DA of DSCTCA for detection of any CAV and significant CAV were 100%, 91.3%, 88.2%, 100%, 94.73% and 100%, 94%, 75%, 100%, 95% respectively. The same on segment-based analysis were 96%, 97.6%, 80%, 99.6%, 97.5% and 100%, 99.6%,86.7%,100%, 99.6%, respectively. There was excellent agreement between the two modalities for detection of any CAV and significant CAV [κ = 0.892 and 0.826 (patient-level), 0.859 and 0.927 (segment-level)]. CAC score correlated significantly with the presence of any CAV on both modalities. A diagnosis of rejection on biopsy did not correlate with any/significant CAV on DSCTCA or ICA. CONCLUSION: High sensitivity and NPV of DSCTCA in the evaluation of stenotic CAV suggests that it can be an accurate and non-invasive alternative to ICA for routine surveillance of HTX recipients. ADVANCES IN KNOWLEDGE: DSCTCA detects the stenotic CAV non-invasively in transplant recipients with high sensitivity, specificity and NPV when compared with catheter coronary angiography, at lower radiation doses. There is excellent agreement between CT angiography and catheter coronary angiography for detection of any CAV and significant CAV. A diagnosis of rejection on biopsy does not correlate with any/significant CAV on CT angiography or catheter angiography.

Congenital Diarrhea and Enteropathies in Infants: Approach to Diagnosis.

Congenital diarrhea and enteropathies (CODEs) are monogenic disorders causing early onset of intractable diarrhea. Their diagnosis and management are challenging. With the availability of commercial next generation genetic testing, we are now better able to classify and manage these disorders. The authors present their experience with 4 cases. Two patients had congenital tufting enteropathy (CTE) and 1 case each of microvillous inclusion disease (MVID) and trichohepatoenteric syndrome (THES). Age at onset varied from 3 to 38 d of life. Light microscopy and electron microscopy of duodenal and rectal endoscopic biopsies were consistent with the diagnosis. Genetic evaluation was possible in 3 cases indicating causative mutations. Two children (CTE and MVID) were alive at last follow-up. The authors suggest a stepwise approach to the diagnosis and management of these disorders in the Indian context.

Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non-small cell lung carcinoma.

BACKGROUND: Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%-85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort. METHODS: This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non-small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and the results were analyzed. RESULTS: Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR-tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed. CONCLUSIONS: Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

Experience of endomyocardial biopsy from a tertiary care center in India.

BACKGROUND: Endomyocardial biopsy is the gold standard and has a definite role in the surveillance of cardiac allograft rejection. Its role in other cardiac diseases is limited. However, it is required for conclusive diagnosis of a few entities in which it can influence patient management. There is no reported data regarding the utility of endomyocardial biopsy in the Indian population. Thus, this study was undertaken in a tertiary care center in India to assess the utility of endomyocardial biopsy in various cardiac diseases in the context of clinical diagnoses. METHODS: All endomyocardial biopsies conducted over a 27-year period were evaluated. Clinical details including indication for biopsy were collected. Histopathological findings were recorded and classified as definitive diagnosis, probable diagnosis with features consistent with the clinical diagnosis, and nonspecific morphological findings. RESULTS: A total of 927 endomyocardial biopsies from 719 patients were reviewed. Endomyocardial biopsy was diagnostic in 12.5% of native cardiac biopsies and 52.1% showed nondiagnostic findings. The most frequent diagnoses were amyloidosis (58.7%) and myocarditis (8.6%). Endomyocardial biopsy had a diagnostic role in evaluation of restrictive cardiac diseases. Endomyocardial fibrosis and tubercular myocarditis, relatively more prevalent in the Indian population, were also identified. Cases of rheumatic heart disease, desmin cardiomyopathy, and microfibrillar cardiomyopathy were surprise findings, proving the usefulness of endomyocardial biopsy in detecting some rare cardiac conditions. CONCLUSION: Endomyocardial biopsy is an important tool for the diagnosis of specific cardiac diseases including some rare entities, and for conditions which are more prevalent in our country, requiring biopsy confirmation.

Thyroid lymphoproliferative lesions in Asia.

Primary thyroid lymphomas (PTLs) are rare and most commonly present as rapidly enlarging thyroid mass causing obstructive symptoms. Due to worldwide differences in clinical practices related to thyroid malignancy, this review was conducted to compare the clinicopathological and diagnostic modalities related to PTL and their similarities and differences between the Asian and Western countries. Using the search engine PubMed, published data on thyroid lymphomas was collected and reviewed. A total of 18 Asian and 22 Western studies were included. Most of PTLs were B-cell Non-Hodgkin lymphomas (NHL). While mucosa-associated lymphoid tissue (MALT) lymphoma was the commonest (41.1%) among Asians, diffuse large B cell lymphoma (DLBCL) (71.9%) predominated in the Western population. Some rare subtypes of PTL were also identified. Majority of all patients in Asian as well as Western studies presented with early stage (stage I/II) disease. Interestingly, when compared with Asian patients, a larger proportion of patients from the West presented with higher stage (stage III/IV) disease (12.2% vs. 3%). Ultrasonography (USG) and fine needle aspiration cytology (FNAC) in addition to histological examination usually by core needle biopsy and in some by open procedures were used for the diagnosis of PTL in both the cohorts. The various ancillary techniques used were immunocytochemistry (ICC), flowcytometry (FC), immunohistochemistry (IHC), and molecular testing. The use of ancillary techniques for PTL diagnosis was more common in the West compared to Asia and markedly increased the sensitivity of cytology to diagnose PTL. Treatment and prognosis largely depend upon the subtype of PTL and stage at presentation. To conclude, from the available published literature, there is an apparent difference between Asian and Western cohorts in the histological type and stage of presentation of PTL, but the results may be affected by publication and selection bias. Also, advanced ancillary techniques are more commonly adopted in the West.

Primary urethral small cell melanoma with neuroendocrine differentiation: a case report.

BACKGROUND: Primary malignant melanoma of the female urethra is an exceedingly rare tumor. It represents 0.2% of all malignant melanomas. Divergent differentiation towards non-melanocytic lineages has not been reported in urethral melanoma. CASE PRESENTATION: We report a rare case of neuroendocrine differentiation in a large primary small cell malignant melanoma involving the urethra, in a 62-year-old lady, who presented with obstructive urinary symptoms. Clinical and radiological workup revealed a large urethral mass with liver and lymph nodal metastases. A biopsy was performed from the urethral and liver lesions which showed poorly differentiated tumor cells with small cell morphology and presence of melanin pigment. These cells were immunopositive for melanocytic and neuroendocrine markers. Ultrastructural examination showed presence of melanosomes and neurosecretory granules in the tumor cells. CONCLUSIONS: Although malignant melanoma with neuroendocrine differentiation is exceptionally rare, it needs to be recognized among the other well-known variants of malignant melanoma.

Cytomorphology of hepatoblastoma with histological correlation and role of SALL4 immunocytochemistry in its diagnosis, subtyping, and prognostication.

BACKGROUND: Hepatoblastoma (HB) is the most common malignant pediatric liver tumor, and cytology material is often the only tissue available for evaluation before definitive therapy. Subcategorization of HB based on cytomorphological features thus carries an important role in its prognostication. Spalt-like transcription factor 4 (SALL4), a marker of embryonic stem cells that is also found in the fetal liver, is reactivated in certain liver tumors. Limited studies have evaluated its role in HB. This study was aimed at evaluating the cytomorphological features of HB and assessing the utility of SALL4 immunocytochemistry (ICC) in its subtyping and prognostication. METHODS: Pretherapy fine-needle aspiration smears from patients diagnosed with HB over a period of 9 years were retrieved. Aspirates were subclassified on the basis of the cytomorphology and were correlated with the histology wherever it was available. ICC for SALL4 was performed in 33 cases, and nuclear staining was considered positive. RESULTS: A total of 53 HB cases were included with 30 available postchemotherapy resection specimens. All the patients were diagnosed as epithelial HB on cytology, and the cases were subclassified as pure fetal (9 of 53), pure embryonal (2 of 53), or combined epithelial HB (42 of 53). There was good concordance between cytology and histology for subtyping. SALL4 immunostaining displayed strong and diffuse nuclear positivity in the embryonal component while focal and weak to negative staining in fetal cells. CONCLUSIONS: Fine-needle aspiration cytology serves as a rapid and effective tool for a correct diagnosis of HB before the implementation of chemotherapy, and SALL4 may serve as a useful diagnostic and prognostic marker.

Epidermal growth factor receptor mutation status in pulmonary adenocarcinoma: Multi-institutional data discussion at national conference of "Lung Cancer Management in Indian context".

The presence of activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in adenocarcinomas of lung confers sensitivity to tyrosine kinase inhibitor therapy. The prevalence of EGFR mutations varies among different ethnicities and demographic profile. This multi-institutional data was compiled to determine the EGFR mutation status in Indians patients with lung adenocarcinoma. Cohorts represented by 4 tertiary care hospitals participated in data discussion at a national conference entitled as 'Lung Cancer Management in Indian Context'. The clinicopathologic data and EGFR mutation rate in the patients of lung adenocarcinoma screened in these cohorts were collected and analyzed. The sample types included both surgical and cytological specimens. A variety of methods were used including immunohistochemistry, polymerase chain reaction, Sanger sequencing and next generation sequencing. A total of 3436 cases of treatment naïve lung adenocarcinoma were tested for EGFR mutations. The overall frequency of EGFR mutations observed was 30.03%. The most common baseline mutation detected was exon 19 deletion followed by L858R point mutation in exon 21. Dual mutations were observed in 6.5% of cases and were predominantly combinations of exon 19 deletion and T790M point mutation in exon 20. Incidence of EGFR mutations was higher among females and non-smokers diagnosed with lung adenocarcinomas. The most common histology in EGFR mutant cases was acinar predominant adenocarcinomas. With nearly one-third of Indian patients with lung adenocarcinoma harboring EGFR mutations, routine testing for these mutations is important to get the benefit of targeted therapy.

Insulinoma-associated protein 1 is a robust nuclear immunostain for the diagnosis of small cell lung carcinoma in cytology smears.

BACKGROUND: In a significant percentage of patients with small cell lung carcinoma (SCLC), cytology samples represent the only source of tumor tissue. Ancillary immunocytochemistry (ICC) for neuroendocrine markers is an important adjunct for the diagnosis of SCLC. Insulinoma-associated protein 1 (INSM1) is a novel neuroendocrine marker proposed as an economical single-marker alternative to the traditional 3-marker panel of chromogranin, synaptophysin, and CD56. To the authors' knowledge, limited studies have evaluated INSM1 immunohistochemistry (IHC) for the diagnosis of SCLC and reported high sensitivities and specificities. The objective of the current study was to evaluate the sensitivity and specificity of INSM1 ICC on direct smears (DS) from patients with SCLC in comparison with IHC on small biopsies (SBs). METHODS: All available DS and SBs from patients with SCLC who were diagnosed over the previous year were retrieved. Immunostaining for INSM1 was performed on alcohol-fixed DS and formalin-fixed SBs wherever available. A total of 10 DS and SBs from patients with non-small cell lung carcinoma were included for comparison. Nuclear staining for INSM1 in ≥1% tumor cells was interpreted as positive. RESULTS: Among a total of 60 patients with SCLC who were included in the current study, a total of 37 underwent INSM1 IHC on SBs and 36 underwent INSM1 ICC on DS. ICC was noninterpretable in 3 DS due to necrosis. The sensitivity of INSM1 IHC was 97% (36 of 37 cases) whereas the sensitivity of INSM1 ICC was 91% (30 of 33 cases) for the diagnosis of SCLC. Among matched IHC and ICC results available for 11 patients, 91% of cases (10 of 11 patients) demonstrated concordant IHC-ICC staining. All cases of non-small cell lung carcinoma were negative for INSM1 (100% specificity). CONCLUSIONS: INSM1 appears to be a robust and reliable ICC marker for the confirmation of SCLC diagnosis on cytology smears.